Efficacy of Late Hematopoietic Stem Cell Mobilization 35-40 Hours after Administration of Plerixafor

Background: Plerixafor with granulocyte stimulating factor (G-CSF) is effective for Peripheral Blood CD34+ stem cell (PBSC) mobilization in patients with poor marrow reserve.  Plerixafor labeling requires administration 11 hours (hrs) before apheresis. Studies show administration of Plerixafor + G-CSF results in peak PBSC concentration 10-14 hrs later. Limited data is available on PBSC count beyond the 14 hr period, though a recent study showed successful mobilization 17 hrs after administration. This allows for a convenient afternoon dosing for apheresis the next morning. There is no data on the effect of Plerixafor on PBSC collection beyond the day after drug administration.

Methods: We studied PBSC collection in seven patients with diagnosis of Multiple Myeloma(5) or NHL (2) who received Plerixafor for low PBSC count < 10/µl (5) or low PBSC collection despite CD34+ count >10/µl(2). All patients had been heavily pretreated with ≥3 chemotherapy regimens (6/7) or had received chemotherapy associated with high risk of mobilization failure (1/7). Mobilization regimen consisted of G-CSF (1), Cyclophosphamide + GCSF (1) or combination chemotherapy + GCSF (5). Patients failing collection received Plerixafor 0.24mg/kg s/c with G-CSF at 10mcg/kg s/c daily with apheresis 11- 16 hrs later till target PBSC count was obtained. Patients then received G-CSF at 10mcg/kg s/c without Plerixafor and underwent another apheresis the following day 35-40 hrs after administration of last dose of Plerixafor.

Results: Patients received Plerixafor beginning day 15-19 in patients receiving combination chemotherapy, day 14 in patient receiving Cyclophosphamide and day 6 in patient receiving G-CSF alone. Total number of Plerixafor dose(s) received for each patient was 1 to 4 (median 3). Average daily collection 11-16 hrs post Plerixafor + G-CSF for individual patients ranged from 0.49 to 4.21 PBSC/kg/day with a mean of 1.20 PBSC/kg/day. PBSC collection 11-16 hrs after the last dose of Plerixafor + GCSF ranged from 0.37 to 4.21 PBSC/kg (mean 2.01). Collection 35-40 hrs post last dose of Plerixafor ranged from 0.41 to 5.25 PBSC /kg (mean 2.35). All patients collected more PBSC in the 35-40 hr time frame compared to the 11-16 hr period. The increment in collection in the 35-40 hr period was from 0.01 PBSC/kg to 1.04 PBSC/kg with a mean increase of 0.34 PBSC/kg. The patient who received G-CSF alone with no chemotherapy, collections 11 hrs and 35 hrs post Plerixafor were 0.73 PBSC/kg and 1.40 PBSC/kg respectively.

Discussion: Successful hematopoietic stem cell mobilization with G-CSF alone was obtained 35-40 hrs beyond last dose of Plerixafor administration. There is need for further pharmacodynamic studies on Plerixafor and CD34+ cell count beyond the conventional 11-14 hr window. Temporal adjustments in Plerixafor administration can result in significant cost savings and improved convenience in PBSC mobilization.